Effects of Atrioventricular Nodal Ablation on Permanent Atrial Fibrillation Patients With Cardiac Resynchronization Therapy: A Systematic Review and Meta‐analysis

Abstract

Cardiac resynchronization therapy (CRT) is a well‐established therapy for patients with heart failure (HF) and wide QRS configuration, especially for those in sinus rhythm. However, for those with permanent AF, atrioventricular nodal (AVN) ablation use remains under debate. Our objective was to evaluate clinical outcomes and mortality of AVN ablation in HF patients with permanent AF receiving CRT. Electronic publication database and reference lists through October 1, 2013 were searched. Observational cohort studies comparing CRT patients with AF who received either AVN ablation or medical therapy were selected. Outcomes included mortality, CRT nonresponse, changes in left ventricular remodeling, and functional outcomes, such as New York Heart Association (NYHA) functional class, quality of life, and 6‐minute hall walk distance. Of 1641 reports identified, 13 studies with 1256 patients were included. Among patients with permanent AF and insufficient biventricular pacing (<90%), those who had undergone AVN ablation compared to those who did not had numerically lower all‐cause mortality (risk ratio [RR]: 0.63, 95% confidence interval [CI]: 0.42 to 0.96, P = 0.03) and significantly lower nonresponse to CRT (RR: 0.41, 95% CI: 0.31 to 0.54, P < 0.00001). Furthermore, AVN ablation was not associated with additional improvements on left ventricular ejection fraction, NYHA functional class, 6‐minute hall walking distance, and quality of life. In patients with permanent AF undergoing CRT, AVN ablation tended to reduce mortality potentially and improved clinical response when it was applied to patients with inadequate biventricular pacing (<90%). Randomized controlled trials are needed to further address the efficacy of AVN ablation among this population.

Introduction

In drug refractory heart failure (HF), cardiac resynchronization therapy (CRT) is an established therapy for patients in sinus rhythm (SR) with severely reduced left ventricular ejection fraction (LVEF) (≤35%) and broad QRS configuration.1, 2 However, patients with atrial fibrillation (AF) are not well represented because of prespecified exclusion from landmark trials on CRT efficacy,3 even though AF is known to predispose or coexist with HF as twin epidemics, and AF prevalence is directly related to HF severity.4 Limited observational studies5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 2 meta‐analyses15, 16 indicated a benefit, albeit to a lesser degree, of CRT in HF patients with AF; however, AF with loss of atrioventricular (AV) synchrony and inadequate biventricular pacing (BiVP)17, 18, 19, 20 potentially undermines CRT efficacy.

Atrioventricular nodal (AVN) ablation, yielding nearly 100% BiVP and regular ventricular rhythm by complete AV block, led to its recommendation by current guidelines (class IIA evidence level).1 In the past decades, increasing evidence underscored the additional benefit provided by AVN ablation in AF patients receiving CRT for HF.6, 7, 8, 21 However, use of the procedure had been limited by its irreversible nature and possible long‐term consequences. Whether AVN ablation should always be considered as a fundamental step in a combined strategy to obtain better outcomes or as backup for medical therapy failure to ensure sufficient biventricular capture remains an inadequately addressed question.

Given the lack of data from clinical trials,6, 7, 8, 9, 11, 12, 13, 14, 22, 23, 24, 25 we performed a systematic review and meta‐analysis of observational studies to evaluate the utility of performing AVN ablation in CRT recipients with permanent AF.

Methods

Search Strategy and Selection Criteria

We searched for articles in any language using MEDLINE, Embase, and Cochrane Central Register of Controlled Trials database of systematic review up to October 1, 2013. The search items included: (1) BiVP OR cardiac resynchronization therapy AND (2) atrial fibrillation. We also checked citations in existing reviews and in all studies identified by the abovementioned methods. Furthermore, the websites of the American College of Cardiology (www.cardiosource.org/acc), the American Heart Association (www.americanheart.org), the European Society of Cardiology (www.escardio.org), Transcatheter Cardiovascular Therapeutics (www.tctmd.com), and EuroPCR (www.europcr.com) were searched for pertinent abstracts and expert presentations. Articles were chosen if the studies: (1) enrolled patients with HF symptoms and permanent AF, left ventricularejection fraction (LVEF) ≤0.35, and QRS duration ≥120 ms, and excluded patients with high ventricular rate or paroxysmal AF; (2) allowed for comparisons between patients with vs those without AVN ablation; (3) reported original data; (4) enrolled at least 25 patients; and (5) had a minimum follow‐up of 6 months. All included studies required patients to be on stable, optimal combination medical therapy for HF before enrollment including β‐blockade, angiotensin inhibition, and use of diuretics.

Data Extraction

Two investigators independently appraised articles (see Supporting Information, Appendix A, in the online version of this article for further description of retrieval methods) and extracted data on study characteristics including design, patient characteristics, AF definition, follow‐up scheme, ablation criteria, and reported outcomes. End points of interest included all‐cause mortality, ejection fraction, change in New York Heart Association (NYHA) class, and functional outcomes, such as 6‐minute hall walk test (6MWT) and quality of life. Finally, data relevant to study quality were extracted using a published framework for rating the validity of observational studies. Study quality for each trial was measured using a standardized protocol and reporting form.27 Disagreements were resolved by consensus.

Statistical Analysis

RevMan 5.0.23 software (The Cochrane Collaboration, Oxford, United Kingdom) and Stata 12 (StataCorp, College Station, TX) were used for meta‐analysis. Mean differences were calculated for continuous variables, and risk ratios were calculated for discontinuous variables. I 2 value describes the proportion of total variation attributable to between‐study differences or heterogeneity because of random error or chance. In the presence of substantial heterogeneity (I ² ≥ 50%), the DerSimonian and Laird random‐effects model was adopted as the pooling method; otherwise, the inverse‐variance fixed‐effects model was used. Sensitivity analysis was performed to check the consistency of the overall effect estimate, and publication bias was examined using a funnel plot.

For trials reporting outcomes at multiple time points, 6‐ or 12‐month follow‐up data were used to ensure comparability among studies. Statistical significance was defined as P < 0.05.

Results

The initial search yielded 1641 results, of which 8 prospective cohort studies,7, 8, 9, 11, 13, 21, 22, 25 4 retrospective studies,6, 12, 14, 24 and 1 abstract23 met inclusion criteria (Table 1). The Table 1 lists the characteristics of the 13 studies published or presented between 2004 and 2013 (see Supporting Information, Appendix B, in the online version of this article for a more comprehensive description of outcomes of the studies). A total of 1256 CRT‐AF recipients was involved, of whom 644 underwent AVN ablation, and 798 were on pharmacological therapy for rate control. Although most studies included 100% of patients with permanent AF, 3 studies included paroxysmal or persistent AF as well.6, 21, 24 AVN ablation was mostly performed after CRT implantation; however, the exact timing differed among studies. The mean follow‐up was 18 months. Among 8 studies that reported the use of an implantable cardioverter defibrillator (ICD), 541 out of 1005 used a CRT defibrillator (CRT‐D). All studies were based on observational cohorts.

Table 1.

Thirteen Studies and Patient Characteristics

Study Author, Year	Design	Inclusion Criteria	Sample Size		Mean Age, y	Male	Permanent AF	Mean Follow‐up	ICD	Ablation Criteria	Outcome
Molhoek, 2004	+	Drug‐refractory HF, NYHA III–IV, LVEF ≤35%, QRS duration ≥120 ms	SR	30	68 ± 8	80	100% persistent AF	18 ± 6 months	—	Not reported	Clinical outcome
			AVNA+	17	63 ± 10 a	90 a			—
			AVNA−	13					—
Gasparini, 2006 b	+	Drug‐refractory HF, NYHA ≥ II, LVEF ≤35%, QRS duration ≥120 ms	SR	511	63 ± 10	77.3	100% permanent AF	25.2 ± 18 months	58.5	BiVP% <85%	Clinical outcome
			AVNA+	114	67 ± 9	86.8			48.8
			AVNA−	48	64 ± 6	83.3
Tolosana, 2008	0	Drug‐refractory HF, NYHA III–IV, LVEF ≤35%, QRS duration ≥120 ms	SR	344	67 ± 9	87 a	100% permanent AF	12 months	52	Poor rate control	Clinical outcome, mortality
			AVNA+	19	69 ± 7				63 a
			AVNA−	107	68 ± 10				—
Ferreira, 2008	0	Drug‐refractory HF, NYHA ≥ II, LVEF ≤35%, QRS duration ≥120 ms	SR	78	66 ± 10	74	Contains all kinds of AF, not listed for each	6 months	76	Inadequate BiVP% or ICD shocks	Clinical outcome, mortality
			AVNA+	26	67 ± 9	92			77
			AVNA−	27	70 ± 8	96			85
Gasparini, 2008 b	+	−	SR	1042	63 ± 9	75	100% permanent AF	Median follow‐up of 34 months	57.8	BiVP% <85%	Mortality
			AVNA+	118	67 ± 9	86			40.7
			AVNA−	125	66 ± 9	78			55.2
Schutte, 2009	0	Drug‐refractory HF, NYHA III–IV, LVEF ≤35%, LBBB QRS duration ≥120 ms	SR	64	70 a	86 a	100% permanent AF	11 ± 0.34 months	—	BiVP% <90%	Clinical outcome
			AVNA+	27					—
			AVNA−	9					—
Dong, 2010	+	Drug‐refractory HF, symptom, LVEF ≤35%, QRS duration ≥120 ms	AVNA+	45	72 ± 9	84	88% permanent AF	274 days	100	Poor rate control	Clinical outcome, mortality
			AVNA−	109	68 ± 11	87		222 days	100
Tolosana, 2012	+	Drug‐refractory HF, NYHA ≥ III, LVEF ≤35% QRS duration ≥120 ms	SR	156	66 ± 9	77	100% permanent AF	12 months	87	BiVP% <85%	Clinical outcome, mortality
			AVNA+	13	68 ± 10	84			76
			AVNA−	33	67 ± 9	67			61
Himmel, 2012	+	Drug‐refractory HF, NYHA III–IV, LVEF ≤35%, QRS duration ≥120 ms	SR	230	69 ± 9	—	100% permanent AF	12 ± 3 months	—	BiVP% <80%	Clinical outcome
			AVNA+	15	70 ± 7	—			—
			AVNA−	31	69 ± 9	—			—
Tolosana, 2013	+	Drug‐refractory HF, NYHA III–IV, LVEF ≤35%, QRS duration ≥120 ms	AVNA+	76	70 ± 8	82	100% permanent AF	At 12, 24, 36, and 60 months	49	BiVP% <85%	Clinical outcome, mortality
			AVNA−	79	68 ± 8	81			62
Eisen, 2013	0	Not specifically reported, average NYHA III, LVEF ≤35%, QRS duration >120 ms,	SR	109	68 ± 11	78.8	47% permanent AF	At 12 and 24 months	64.2	—	Clinical outcome, mortality
			AVNA+	10	70 ± 13	78.9			48.5
			AVNA−	56
Jedrzejczyk, 2013	+	Drug‐refractory HF, NYHA III–IV, LVEF ≤35%, QRS duration ≥120 ms	SR	120	—	—	100% permanent AF	Median follow‐up of 36.1 months	—	BiVP% <95%	Mortality outcome
			AVNA+	40	—	—			—
			AVNA−	40	—	—			—
Jedrzejczyk, 2010 (abstract)	—	Not specifically reported, average NYHA III, LVEF ≤35%, QRS duration >120 ms	AVNA+	15	—	—	—	6 months	—	—	Clinical outcome
			AVNA−	44	—	—

Abbreviations: AF, atrial fibrillation; AVN, atrioventricular nodal; AVNA+, patients who had undergone AVN ablation; AVNA−, patients who did not undergo AVN ablation; BiVP, biventricular pacing; HF, heart failure; ICD, implantable cardioverter defibrillator; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; SR, sinus rhythm.

^— indicates that information was not reported, + indicates prospective design, and 0 indicates retrospective design.

^aTrials did not report separate information for the AF subgroup.

^bThe 2 articles by Gasparini included duplicate patients but assessed different outcomes.

The quality of the studies included is limited by the fact that the majority are observational cohort studies instead of randomized trials. The inclusion criteria for enrollment were similar across studies. Measures of study quality are performed by a composite of features derived from the Newcastle Ottawa Scale. All studies were based on observational cohorts, and 1 study reported significant differences in baseline characteristics.21 Moreover, most studies involved nonblinded assessment of study outcomes and failed to describe follow‐up completeness.

Device Programming and Biventricular Capture

Ventricular rate regulation was adopted in 4 studies,7, 8, 13, 22 2 of which programmed on a “trigger by right ventricular sensing” algorithm.13, 22 Detailed information on device type, such as the choice of CRT‐D or CRT pacemaker (CRT‐P), was not available in most studies. Finally, ventricular rates for AF patients were kept in a narrow range (usually 70 to 90 bpm).

Biventricular capture was recorded from device diagnosis. Ten of the 13 studies described the effectiveness of biventricular capture. Eight‐five percent of pacing burden was used as the cutoff value for adequate BiVP by 4 studies. Mean biventricular capture rates for AF‐CRT patients without AVN ablation ranged from 82%11 to 96%,21 whereas nearly 100% biventricular capture was achieved in patients with AVN ablation.

Mortality

The result of 6 trials suggested adjunctive AVN ablation had significant effect on reducing mortality rate (n = 416, RR: 0.63; 95% CI: 0.42 to 0.96, P = 0.03) (Figure 1). Between‐study heterogeneity for all‐cause mortality was mild (I 2 = 48%). Only 3 studies reported the cause of death for a proportion of patients: the RR for cardiovascular mortality was 0.69 (95% CI: 0.39 to 1.21, P = 0.17), and the heterogeneity was moderate (I ² = 54%).6, 7, 22 The small number of studies included precluded subgroup analysis. However, the study by Tolosana et al14 was significantly different from the other 2.

Figure 1.

Meta‐analysis of studies comparing the relative risk (RR) of all‐cause (A) and cardiovascular (B) mortality among patients with atrial fibrillation who underwent vs those who did not undergo concomitant AVN ablation. The P value for the pooled RR = 0.001. I ² is proportion of the variation in RR that is due to between‐study heterogeneity. Abbreviations: AF, atrial fibrillation; AVN, atrioventricular nodal; AVNA+, CRT recipients with AF who did undergo AVN ablation; AVNA−, CRT recipients with AF who did not undergo AVN ablation; CI, confidence interval; CRT, cardiac resynchronization therapy; M‐H, Mantel‐Haenszel.

Clinical Response to CRT

Response to CRT was defined as ≥1 class improvement in NYHA and survival over 6 to 12 months,6, 11, 13, 14, 25 ≥10% reduction in left ventricular end‐systolic volume,8, 13 and a 10% improvement in 6MWT.13, 14 There were 221 nonresponders reported in a total of 6 studies.6, 8, 11, 14, 22, 25 The overall mean proportion of responders was 63.6% (range, 48.5%–84.6%) and 46.6% (range, 18.7%–58.8%) among patients with and without AVN ablation, respectively. RRs were calculated using the number of nonresponders among AVNA + and AVNA − patients, respectively; the RR of CRT nonresponse for AVNA + vs AVNA − was 0.67 (95% CI: 0.43 to 1.04, P = 0.08, I ² = 73%). Subgroup analysis was conducted. It was suggested that for those with BiVP% ≤90%, adjunctive AVN ablation was associated with lower risk of CRT nonresponse (RR: 0.41, 95% CI: 0.31 to 0.54, P < 0.00001). For those with relatively sufficient BiVP (>90%), AVN ablation did not make any difference in CRT nonresponse (RR: 0.97, 95% CI: 0.72 to 1.32, P = 0.87) (Figure 2). Furthermore, no significant heterogeneity was detected in both subgroups (I ² = 0).

Figure 2.

Subgroups analysis comparing clinical CRT nonresponse risk of patients with AF who underwent vs those who did not undergo concomitant AVN ablation. Abbreviations: AF, atrial fibrillation; AVN, atrioventricular nodal; AVNA+, CRT recipients with AF who did undergo AVN ablation; AVNA−, CRT recipients with AF who did not undergo AVN ablation; BiVP = biventricular pacing; CI, confidence interval; CRT, cardiac resynchronization therapy; M‐H, Mantel‐Haenszel.

Cardiac Function

LVEF for both groups improved significantly across 9 studies. Patients who underwent AVN ablation experienced a weight improvement in LVEF of 9.7% (95% CI: 8.32 to 11.08), which was 1.39% larger (95% CI: −2.26 to 5.04, P = 0.46) than that in patients without AVN ablation. There was a significant degree of heterogeneity for this outcome (I ² = 81%) (Figure 3).

Figure 3.

Mean difference in LVEF change in patients with AF who underwent vs those who did not undergo AVN ablation. Abbreviations: AF, atrial fibrillation; AVN, atrioventricular nodal; AVNA+, CRT recipients with AF who did undergo AVN ablation; AVNA−, CRT recipients with AF who did not undergo AVN ablation; CI, confidence interval; CRT, cardiac resynchronization therapy; IV, instrumental variables; LVEF = left ventricular ejection fraction.

Other End Points

Insufficient data were available to permit meta‐analysis of hospitalization events in patients with and without AVN ablation. The mean difference in NYHA class improvement favored AVN ablation (RR: −0.1, 95% CI: −0.3 to 0.1, P = 0.35), but it did not reach statistical significance. Similarly, patients who underwent AVN ablation experienced a weighted improvement in 6MWD of 125.2 meters (range, 53–144 meters), which was 16.72 meters (95% CI: 13.42 to 46.85, P = 0.28) larger than that in patients without AVN ablation. Four studies reported quality of life changes based on the Minnesota Living With Heart Failure score. Patients with AVN ablation had improved scores in all studies, with a mean reduction of 17 points (range, 14–19 points); the pooled mean improvement was 0.34 points less than those without AVN ablation (95% CI: −7.05 to 6.36, P = 0.92).

Sensitivity Analysis and Publication Bias

In the part focused on all‐cause mortality, a meta‐analysis adjusting the baseline characteristics was performed after excluding 1 study that enrolled patients with significant differences in primary LVEF and NYHA,21 and no obvious change was identified (RR: 0.71, 95% CI: 0.49 to 1.05); accordingly, relevant heterogeneity was reduced to 37%. In the third part on LVEF, the study heterogeneity was driven by the study of Gasparini et al.8 Removal of this study yielded a slighter LVEF improvement of 0.39% (95% CI: −1.3 to 2.08, P = 0.65), and I 2 was reduced from 81% to 0%. Notably, the method of calculating LVEF was not reported in the standard fashion and could not be compared among studies. Changes in the effect estimate in other sensitivity analyses were all not apparent.

Funnel plots were visually symmetrical in both the first and the fourth groups on all‐cause mortality and LVEF, respectively, suggesting no significant publication bias among the studies (Figure 4).

Figure 4.

Evaluation of publication bias in all‐cause mortality and left ventricular ejection fraction. Abbrivationss: e = standard error.

Discussion

AVN ablation has been a long‐established strategy and maybe the only option in AF for uncontrolled ventricular rate. In permanent AF patients receiving CRT, it also guarantees regular ventricular rhythm. The rate‐vs‐rhythm control strategies have been a crucial decision point in AF patients; however, that does not seem to apply for AF patients with HF because patients enrolled in the latter usually had a longer history of HF and received less antiarrhythmic drugs and more medication for HF. The Atrial Fibrillation and Congestive Heart Failure trial, which enrolled 1376 patients with AF and severe HF, observed no benefit for a rhythm‐control over a rate‐control strategy with respect to mortality and worsening HF, suggesting a rate control strategy as a primary approach.28 An as‐low‐as‐you‐can‐go strategy for rate control has been advocated. The threshold for adequate rate goal remains uncertain. In our analysis of published studies, patients with severely depressed ventricular function achieved controlled ventricular rate between 60 to 80 bpm under resting conditions, which appears reasonable. However, the ventricular rate is not positively correlated with optimal BiVP because of an irregular sequence of RR intervals. The result of RAFT (Resynchronization for Ambulatory Heart Failure Trial)29 revealed that, although patients with permanent AF had to be adequately rate controlled (resting ventricular rate ≤60/min and a ventricular rate <90/min after the 6MWT) before randomization, only one‐third of CRT patients received ≥95% of BiVP. Even this may be an overestimate because the percentage of BiVP recorded by device counters is often artificially inflated during AF due to erroneous counting of the above‐mentioned fusion or pseudofusion complexes,30 which needs further evaluation in appropriately designed studies.

Criteria for AVN ablation for most studies were BiVP rate of lower than 85%. Whether incremental benefits occur beyond a pacing percentage of 85%, 90%, or even greater is uncertain. Koplan et al analyzed 1812 patients undergoing CRT and found that the greatest magnitude of benefit was observed with >92% BiVP.21 The LATITUDE study showed that mortality was inversely associated with the percentage of BiVP, and the greatest magnitude of reduction in mortality was observed with a BiVP cutoff in excess of 98%.19 The current European Society of Cardiology guidelines indicate that a minimum value of ≥95% should be used as optimal.2

A meta‐analysis with similar objectives was previously published.31 Ganesan et al summarized 3 studies and observed a substantial reduction in all‐cause mortality (RR: 0.42, 95% CI: 0.26 to 0.68, P < 0.001) and NYHA improvement, thus suggesting a general adoption for ablation. In our analysis, the 90% threshold seemed to be a determinant factor on whether AVN ablation is mandatory to obtain optimized CRT response, which was the case for patients with BiVP lower than said threshold. A subgroup of patients with BiVP% >90% failed to show any additional benefit of AVN ablation on CRT response (P = 0.49), whereas in their counterparts (BiVP <90%), AVN ablation was favored significantly (P < 0.00001). No additional benefit on ejection fraction and NYHA class were observed. Furthermore, AVN ablation tended to reduce all‐cause mortality (RR: 0.63, 95% CI: 0.42 to 0.96, P = 0.03) in 6 studies. One study by Tolosana et al,14 with a median BiVP of 94% in the non‐AVN ablation group, indicated that instead of ablation, basal NYHA functional class IV, permanent AF, and high creatinine levels were independent predictors of mortality. Jedrzejczyk et al,23 with mean BiVP% controlled above 95%, reported a mortality RR of 0.85. Interestingly, after adjustment for baseline confounders, mortality in the AVN ablation group was even higher. Comparing the 2 studies with desired BiVP above, patients with insufficient BiVP showed greater mortality risk.6, 7 The corresponding RRs for ablation were 0.59 and 0.32, respectively, for groups with BiVP <90% in the nonablation group.6, 21

Recently, AVN ablation became increasingly attractive because it affords the opportunity to guarantee essentially 100% of BiVP, prevent ICD shocks as CRT‐D is widely accepted, and reduce usage of digoxin and amiodarone, which may have a negative effect on morbidity and mortality in patients with HF.32, 33 Although favored, general adoption of an AVN ablation strategy in CRT might not be indicated given concern for the long‐term safety of the procedure. Apart from rare acute complication, such as valve regurgitation, the deleterious effect on long‐term outcomes of the creation of permanent atrioventricular block and pacemaker dependency is a more serious concern.34

The benefit reported with AVN ablation should be interpreted according to different clinical characteristics of patients selected for therapy. Delnoy et al5 showed a clear benefit of CRT in a population of patients with AF, with a minority of patients undergoing AVN ablation. This may have been driven by higher rates of biventricular capture in their study, in which 90% of AF patients achieved >90% biventricular capture. The authors pointed to higher rates of amiodarone prescription, which is not substantially different from that in other prospective trials. Moreover, a small fraction of patients with persistent or permanent AF may in fact convert to SR after several months of CRT due to reverse left ventricular remodeling and reduction of mitral regurgitation. In a meta‐analysis published recently of 3 studies examining the effect of CRT on persistent or permanent AF, the combined rate of conversion from AF to SR was 0.107,35 most probably as a result of the reversal of maladaptive remodeling. Furthermore, some authors have suggested the use of device‐derived features to further optimize response to CRT. Specifically, AV delay programming and biventricular triggering parameters may have a role in improving the percentage of BiVP.20, 30, 36 Meanwhile, it seems reasonable not to perform AVN ablation systematically at the time of CRT implantation, but instead to perform it a few weeks later if BiVP is suboptimal (<95%–99%) despite adequate pharmacological optimization of ventricular heart rate. Results of ongoing randomized studies may further clarify whether AVN ablation should routinely accompany CRT in patients with AF.

Study Limitations

Our analysis was limited by the fact that in the 13 eligible studies from the literature search, 8 were prospective observational cohort studies and 3 retrospective observational cohort studies, which can introduce unwanted selection bias or referral bias. The data extracted were compiled from a limited number of small studies, which may reduce the opportunity for subgroup analyses. Comprehensive data could not be extracted on some clinical features, such as device programming and detailed ventricular rate; documentation of follow‐up completeness also was limited. Furthermore, the decision to undertake AVN ablation and AVN ablation timing were not uniform. Given the small number of patients included in these studies, the analysis may be limited by significant imbalances in baseline patient characteristics between the 2 subgroups and by changes in both medical therapy and AVN ablation over the study period. There was moderate between‐study heterogeneity in the RR of all‐cause and cardiovascular mortality; sensitivity analysis did not alter the interpretation of the results.

Future randomized studies will be important to eliminate patient selection bias. Clinicians should follow the criteria for patient selection in the landmark trials when selecting patients for CRT, extrapolate with caution from these, and be extremely cautious in the interpretation of observational data.

Conclusion

Preliminary series studies showed that AVN ablation in AF patients with CRT provided potential survival benefits and better response for CRT in patients with insufficient BiVP (<90%) compared to those on medical therapy. However, improvement in cardiac function as reflected by LVEF and NYHA, exercise tolerance and quality of life were independent of the procedure. The specific potential benefits and deleterious effects of this strategy remain to be defined in large prospective randomized studies, particularly assessing whether AVN ablation should routinely accompany CRT in patients with permanent AF despite good pharmacologic rate control or whether there exist clearer criteria, especially on BiVP%, for AVN ablation.

Supporting information

AppendixS1. Figure Flow diagram of the trial selection process.

AppendixS2. Table 2 Outcomes for patients included in this systematic review